US20220355040A1 - Devices and methods for precision dose delivery - Google Patents

Abstract

Disclosed herein are delivery devices for delivering a volume of a drug product, placebo product, or other product including a fluid. The devices may include a barrel having a longitudinal axis, a proximal end region, and a distal end region. The proximal end region may include an opening, and the barrel may be configured to receive a drug therein. A plunger rod may be disposed at least partially inside the barrel and protruding from the opening. The plunger rod may include a rack having a plurality of teeth. The device may further include a pinion having a plurality of teeth configured to engage with the plurality of teeth of the rack, and rotation of the pinion against the rack may move at least a part of the plunger rod along the longitudinal axis of the barrel.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS
• This application claims priority to U.S. Application No. 62/598,212, filed Dec. 13, 2017; U.S. Application No. 62/676,047, filed May 24, 2018; and U.S. Application No. 62/722,252, filed Aug. 24, 2018, all of which are incorporated by reference herein in their entireties.
FIELD OF DISCLOSURE
• Aspects of the present disclosure relate to devices and methods for priming or otherwise configuring a dose delivery device, e.g., a syringe, to promote precision dose delivery. More specifically, embodiments of the present disclosure relate to devices and methods for loading, storing, transporting, and/or delivering precise doses of a drug product, placebo product, or other product including a fluid.
INTRODUCTION
• Liquid drug products may be deliverable to patients in a variety of ways, including via injection. In many cases, the precision and accuracy of a liquid drug product's volume is crucial. For example, medical professionals may have an interest in ensuring that an approved or prescribed volume of a drug product is consistently delivered to each patient requiring the drug. Additionally, over- or under-dosing a patient with a drug product, even slightly, may have an undesired (or even negative) clinical impact on the patient. Moreover, some drug products are prescribed at low volumes (e.g., under 100 μL). At low volumes, human error in preparing and delivering an accurate dose of a drug product for injection may impact the drug's efficacy in a patient and the subsequent clinical effect on the patient.
• Additional aspects of liquid drug product delivery can complicate the goal of accurate dose delivery via injection. For example, for a correct dose of a drug product to be dispensed from a device (e.g., a syringe), a corresponding accurate volume of the drug product must be loaded into the device. Furthermore, handling, storage, packaging, and/or transportation of loaded devices must not result in inadvertent expulsion of drug product from the devices. Additionally, prior to administration of a drug product from a device, the device may need to be primed to remove air bubbles from within the device's needle and barrel. Incorrectly priming a device may result in expulsion of too much or too little drug product from the device, which likewise may result in a decreased dose being delivered to a patient, or air bubbles being injected from the device into the patient.
SUMMARY
• Disclosed herein are fluid delivery devices. In an aspect of the present disclosure, the devices may include a barrel having a longitudinal axis, a proximal end region, and a distal end region. The proximal end region may include an opening, and the barrel may be configured to receive a drug therein. A plunger rod (having a piston coupled thereto) may be disposed at least partially inside the barrel and protruding from the opening. The plunger rod may include a rack having a plurality of teeth. The device may further include a pinion having a plurality of teeth configured to engage with the plurality of teeth of the rack, and rotation of the pinion against the rack may move at least a part of the plunger rod along the longitudinal axis of the barrel.
• Various aspects of the device may include one or more of the features below. The device may also include a shaft affixed to the pinion, wherein rotation of the shaft rotates the pinion against the rack. In one embodiment, a knob may be affixed to the shaft. In another embodiment, a visualization device (e.g., a magnifier) may be disposed on the distal end region of the barrel. In a further embodiment, the device may include a stopper inside the barrel, and the stopper may be affixed to a distal end of the plunger rod. In an exemplary embodiment, the device may further include a circular ratchet disposed coaxially with the pinion, wherein the circular ratchet has a diameter smaller than a diameter of the pinion, a spring-loaded pawl disposed on an internal circumference of the pinion, wherein the pawl is configured to engage the ratchet, and a shaft affixed to the ratchet, wherein rotation of the shaft in one direction causes rotation of the pinion, and rotation of the shaft in a second direction does not cause rotation of the pinion. In some embodiments, the ratchet may be disposed inside the pinion. In some embodiments, the pinion may include a plurality of teeth having a first height, and a stopper tooth having a second height greater than the first height. In further embodiments, the second height of the stopper tooth may prevent the pinion from engaging the plurality of teeth of the rack. In still further embodiments, the second height of the stopper tooth may be configured to contact one of the plunger rod and the rack to stop rotation of the pinion. In still other embodiments, the plunger rod may include an inner column and an outer lumen, and the rack may be disposed on the inner column. In some embodiments, rotation of the pinion against the rack may move the inner column of the plunger rod independently of the outer lumen. In some embodiments, the device may also include a shaft removably affixed to the pinion, wherein the shaft prevents movement of the outer lumen of the plunger rod relative to the barrel, and wherein removal of the shaft allows for movement of the outer lumen of the plunger rod relative to the barrel.
• In some embodiments, the plunger rod may further include a body and a flange, the flange extending partially along a longitudinal length of the body and having a width greater than a width of the body, and the barrel may further include a plunger lock, the plunger lock including a through hole configured to allow the flange to pass through the second plunger lock in a specific orientation.
• In another aspect of the present disclosure, a drug delivery device may include a barrel having a longitudinal axis, a proximal end region, a distal end region, and an interior, the proximal end region including an opening and the interior including a threaded region. The device may further include a plunger rod disposed at least partially inside the barrel and protruding from the opening, the plunger rod having a threaded region configured to engage the threaded region of the barrel interior. Rotation of the plunger rod about the longitudinal axis of the drug delivery device may move the plunger rod along the longitudinal axis.
• Various aspects of the device may include one or more of the features below. The plunger rod may further include a tab protruding from the plunger rod in a first direction and located proximally from the threaded region of the plunger rod, and the threaded region in the interior of the barrel may further include a slot sized and configured to allow for the tab to pass through the threaded region in the interior of the barrel. In some embodiments, the slot may include a first segment parallel to the longitudinal axis of the drug delivery device and a second segment perpendicular to the longitudinal axis of the drug delivery device. In some embodiments the slot may include a third segment parallel to the longitudinal axis of the drug delivery device, wherein the second segment is in between the first segment and the third segment. In other embodiments, the tab is a first tab, and the plunger rod may further include a second tab protruding from the plunger rod in a second direction opposite to the first direction, and the threaded region in the interior of the barrel may further include a second slot sized and configured to allow for the second tab to pass through the threaded region in the interior of the barrel.
• In another aspect of the present disclosure, a drug delivery device may include a barrel having a proximal end region, a distal end region, an opening in the proximal end region, an interior, and a threaded region in the interior. The device may further include a sleeve disposed partly inside the barrel and protruding from the opening in the proximal end region of the barrel, the sleeve including a threaded region engaged with the threaded region of the barrel interior. The device may also include a plunger rod disposed at least partially inside the sleeve, and a stopper inside the barrel and located distally from the sleeve, the stopper connected to a distal end of the plunger rod. Rotation of the sleeve in a first direction around a longitudinal axis of the drug delivery device may move the sleeve towards the distal end region of the barrel.
• Various aspects of the device may include one or more of the features below. Rotation of the sleeve in the first direction may move the stopper towards the distal end region of the barrel. In some embodiments, the sleeve may include an inner passage, and the stopper may have a diameter larger than a diameter of the inner passage. In some embodiments, the sleeve may include a tab disposed on an exterior of the sleeve, the tab may be located proximally from the threaded region of the barrel interior, and the tab may stop movement of the sleeve towards the distal end region of the barrel. In further embodiments, the tab may be configured to stop movement of the sleeve towards the distal end region of the barrel after the drug delivery device has been primed. In additional embodiments, the tab may be a first tab, the sleeve may further include a second tab disposed on an exterior of the sleeve, the second tab may be located distally from the threaded region of the barrel interior, and the second tab may stop movement of the sleeve towards the proximal end region of the barrel.
• In a further aspect of the present disclosure, a drug delivery device may include a barrel having a proximal end region and a distal end region, and the proximal end region may include an opening. The device may also include a plunger rod having a body and a flange, the flange extending partially along a longitudinal length of the body and having a width greater than a width of the body, the plunger rod being disposed at least partially inside the barrel and protruding from the opening. The device may also include a first plunger lock disposed on the barrel, the first plunger lock being configured to block the flange from entering the barrel, and a second plunger lock disposed in the barrel, the second plunger lock including a through hole configured to allow the flange to pass through the second plunger lock in a specific orientation.
• Various aspects of the device may include one or more of the features below. In some embodiments, the first plunger lock may be removable. In some embodiments, the first plunger lock may be frangible. In still other embodiments, a distance between the first plunger lock and the second plunger lock may be equivalent to the distance that the stopper must travel to prime the drug delivery device. In other embodiments, the plunger rod may be rotatable around a longitudinal axis of the drug delivery device.
• In a further aspect of the present disclosure, a method of dispensing a substance from a drug delivery device having a plunger rod and a barrel may include advancing the plunger rod by a predetermined distance into the barrel until advancement of the plunger rod is resisted by a stop, deactivating the stop, and actuating the plunger rod to deliver the substance.
• Various aspects of the device may include one or more of the features below. In some embodiments, advancing the plunger rod may comprise rotating a pinion against a rack disposed on the plunger rod. In some embodiments, the stop may comprise a shaft removably affixed to the pinion, and deactivating the stop may comprise removing the shaft from the pinion. In still other embodiments, deactivating the stop may comprise rotating the plunger rod. In some embodiments, the plunger rod may comprise a flange, and the stop may comprise a lock that prevents the flange from entering the barrel. In other embodiments, deactivating the stop may comprise removing the lock. In some embodiments, deactivating the stop may comprise breaking the lock.
BRIEF DESCRIPTION OF THE DRAWINGS
• The accompanying drawings, which are incorporated into and constitute a part of this specification, illustrate various exemplary embodiments and, together with the description, serve to explain principles of the disclosed embodiments. The drawings show different aspects of the present disclosure and, where appropriate, reference numerals illustrating like structures, components, materials, and/or elements in different figures are labeled similarly. It is understood that various combinations of the structures, components, and/or elements in various embodiments, other than those specifically shown, are contemplated and are within the scope of the present disclosure.
• There are many embodiments described and illustrated herein. The described devices and methods are neither limited to any single aspect nor embodiment thereof, nor to any combinations and/or permutations of such aspects and/or embodiments. Moreover, each of the aspects of the described inventions, and/or embodiments thereof, may be employed alone or in combination with one or more of the other aspects of the described inventions and/or embodiments thereof. For the sake of brevity, certain permutations and combinations are not discussed and/or illustrated separately herein.
• FIG. 1 depicts an exemplary delivery device (e.g., a syringe), according to one embodiment of the present disclosure.
• FIG. 2 depicts an exemplary pawl and ratchet mechanism for a delivery device, according to one embodiment of the present disclosure.
• FIGS. 3A and 3B depict an exemplary lock mechanism for a delivery device, according to one embodiment of the present disclosure.
• FIGS. 3C and 3D depict an exemplary telescoping mechanism for a delivery device, according to one embodiment of the present disclosure.
• FIGS. 4A and 4B depict exemplary rotational lock mechanisms for a delivery device, according to embodiments of the present disclosure.
• FIGS. 4C-4E depict an exemplary delivery device with an exemplary rotational lock mechanism in various positions, according to an embodiment of the present disclosure.
• FIG. 5 depicts an exemplary delivery device, according to one embodiment of the present disclosure.
• FIGS. 6A-6E depict an exemplary delivery device and locking mechanism, according to one embodiment of the present disclosure.
• FIG. 7A depicts an exemplary delivery device, according to one embodiment of the present disclosure.
• FIG. 7B depicts a threaded portion of the delivery device ofFIG. 7A.
• FIG. 8 depicts an alternative embodiment of the threaded portion ofFIG. 7B.
• FIG. 9A depicts an exemplary delivery device, according to one embodiment of the present disclosure.
• FIGS. 9B-9D depict locking components of the delivery device ofFIG. 9A.
• FIGS. 10A-10C depict further exemplary delivery devices according to additional embodiments of the present disclosure.
• FIGS. 11A and 11B depict still further exemplary delivery devices according to additional embodiments of the present disclosure.
• FIG. 12 depicts an exemplary delivery device according to additional embodiments of the present disclosure.
• FIGS. 13A-13C depict an exemplary priming and delivery mechanism for a delivery device according to additional embodiments of the present disclosure.
• FIGS. 14A-14C depict another exemplary priming and delivery mechanism for a delivery device according to additional embodiments of the present disclosure.
• FIGS. 15A-15E depict another rotational lock mechanism for a delivery device according to additional embodiments of the present disclosure.
• FIGS. 16A-16E depict another exemplary delivery device and lock mechanism, according to additional embodiments of the present disclosure.
• FIGS. 17A-17C depict further exemplary delivery devices and mechanisms according to additional embodiments of the present disclosure.
• FIGS. 18A-18F depict a locking and priming mechanism for a delivery device according to additional embodiments of the present disclosure.
• FIGS. 19A-19E depict another locking and priming mechanism for a delivery device according to additional embodiments of the present disclosure.
• FIGS. 20A-20C depict another locking and priming mechanism for a delivery device according to additional embodiments of the present disclosure.
• As used herein, the terms “comprises,” “comprising,” “includes,” “including,” or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements, but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. The term “exemplary” is used in the sense of “example,” rather than “ideal.” Notably, an embodiment or implementation described herein as an “example” or “exemplary” is not to be construed as preferred or advantageous, for example, over other embodiments or implementations; rather, it is intended reflect or indicate the embodiment(s) is/are one “example,” rather than “ideal.” In addition, the terms “first,” “second,” and the like, herein do not denote any order, quantity, or importance, but rather are used to distinguish an element, a structure, a step or a process from another. Moreover, the terms “a” and “an” herein do not denote a limitation of quantity, but rather denote the presence of one or more of the referenced items.
DETAILED DESCRIPTION
• Embodiments of the present disclosure may be used in addition to and/or in combination with aspects of U.S. provisional application No. 62/598,212, which in incorporated by reference in its entirety herein.
• Embodiments of the present disclosure may be used with any type of fluid-containing products, such as liquid drug products, liquid placebos, or other liquids that may be dispensed in a dose form. In some embodiments, drug products may include one or more active ingredients, including, e.g., small or large molecules or biologics, such as pain medications, steroids, or biologics. As used herein, the term “biologic” may refer to a large molecule (e.g., having a size greater than 15 kDa, greater than 30 kDa, greater than 50 kDa, greater than 75 kDa, or greater than 100 kDa) created in a living system such as a cell. Biologics may include proteins (e.g., antibodies), nucleic acids, large sugars, etc. Unlike small molecules that may have well-defined chemical structures, biologics may have highly complex structures that cannot be easily quantified by laboratory methods. As used herein, the term “drug product” may refer to a volume of a formulated drug substance apportioned into a primary packaging component for packaging, transportation, delivery, and/or administration to a patient.
• The term “primary packaging component” refers to a packaging component for a drug product, such as a drug container, that is designed and manufactured to be in direct physical contact with the formulated drug substance. (See, for example, Guidance for Industry on Container Closure Systems for Packaging Human Drugs and Biologics, U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research, and Center for Biologics Evaluation and Research (May 1999), which is incorporated by reference herein.) Examples of primary packaging components include prefillable syringes, Luer syringes, cartridges, and vials made of glass, plastic, and/or other materials.
• Embodiments of the present disclosure may be used with products typically having small dose volumes, such as, e.g., ophthalmic drug products. In some embodiments, devices of the present disclosure may be used with drug products including an antigen-binding molecule. In some aspects, the antigen-binding molecule may be an antibody or antigen-binding fragment. In some embodiments, devices of the present disclosure may be suitable for use with drug products including ingredients such as, e.g., aflibercept, alirocumab, abicipar pegol, bevacizumab, brolucizumab, conbercept, dupilumab, evolocumab, tocilizumab, certolizumab, abatacept, rituximab, infliximab, ranibizumab, sarilumab, adalimumab, anakinra, trastuzumab, pegfilgrastim, interferon beta-la, insulin glargine [rDNA origin], epoetin alpha, darbepoetin, filigrastim, golimumab, etanercept, antigen-binding fragments of any of the above, or combinations of such binding domains, such as a bispecific antibody to VEGF or angiopoietin-2, among others.
• For some products in particular, e.g., ophthalmic or other drug products, dose accuracy may be particularly important. However, it is also contemplated that embodiments of the present disclosure may be applicable to any other liquid products or any other context for which precise methods for setting and administering a reliably accurate dose or delivery volume are beneficial.
• In some embodiments, devices according to the present disclosure may be manufactured, packaged, filled, and/or otherwise prepared according to processes relevant to the products (e.g., drug products) they may be used with. For example, in some embodiments, devices according to the present disclosure may be sterilized, either before or after being filled and/or packaged. For example, in some embodiments, devices according to the present disclosure may be filled and packaged in, e.g., blister packaging, and/or may be terminally sterilized using any suitable method in the art. For example, devices according to the present disclosure may be terminally sterilized using a chemical sterilization method, such as a method including ethylene oxide or hydrogen peroxide (e.g., vaporized hydrogen peroxide). In some embodiments, devices according to the present disclosure may be terminally sterilized using methods described in, e.g., International Application No. PCT/US2018/021013, filed Mar. 6, 2018, which is incorporated by reference herein in its entirety.
• Dose delivery devices available on the market, such as prefilled syringes or syringes for use with vials, may not necessarily assist with accurately loading a desired volume of a product, priming the devices, expelling excessive drug product from the devices, and/or removing air bubbles from the devices. In dose delivery devices containing a small volume of a drug product in particular (e.g., about 500 μL or less, about 300 μL or less, about 250 μL or less, about 200 μL or less, about 150 μL or less, about 100 μL or less, about 50 μL or less, or about 25 μL or less, such as between about 25 μL and about 50 μL, between about 50 μL and about 100 μL, between about 25 μL and about 100 μL, between about 50 μL and about 150 μL, between about 100 μL and about 250 μL, between about 100 μL and about 150 μL, between about 150 μL and about 250 μL, between about 200 μL and about 250 μL, between about 200 μL and about 500 μL, or between about 250 μL and about 500 μL), it may also be difficult to confirm the presence of the correct dose of a drug product in the device with the naked eye. Currently in the dose delivery device market, and specifically in the syringe market, there is a need for mechanisms that allow a user to set precisely for delivery a small volume of a product in a syringe (e.g., a prefilled or fillable/refillable syringe), prime the syringe, remove air bubbles from the syringe, and/or confirm or be assured that the dose volume in the syringe is correct. Embodiments of the present disclosure may assist manufacturers, drug product providers, medical professionals, and/or patients with accurately filling or otherwise preparing a dose administration device, priming the device, removing bubbles from the device, confirming the dose, and/or administering a dose from the device to a patient. Moreover, embodiments of the present disclosure may assist in preventing or mitigating errors or variation in device manufacture or use, such as errors or variation in placement of dose lines on devices, variation in device geometry (e.g., variation in syringe neck geometry), and/or variation or errors in setting a dose line prior to delivery of a product.
• In some instances, embodiments of the present disclosure may be of particular assistance to individuals who may have difficulty setting doses with precision and accuracy. For example, embodiments of the present disclosure may assist elderly individuals, young children, or persons with physical or mental disabilities in setting accurate doses.
• Described herein are various embodiments for dose delivery devices, and in particular, for syringes. In some instances, embodiments disclosed herein may be used in conjunction with existing syringe body parts to modify off-the-shelf products, which may reduce the development and manufacturing time for the dose delivery devices. In other instances, embodiments disclosed herein may be included in devices during their manufacture. The syringes described herein may be prefilled or may be fillable/refillable.
• Embodiments of the present disclosure may include syringes having rotating parts, threaded parts, springs, gears, and the like, that may allow a user to precisely control the movement of dosage setting and delivery elements such as, e.g., plungers and/or stoppers. In some embodiments, for example, screw and gear mechanisms may be used to transfer rotary motion (e.g., on a knob or dial) to linear motion of a plunger, and thus to set the plunger rod of a syringe to a predefined position with reduced human effort and/or relatively greater accuracy. By reducing human effort and/or increasing accuracy, it is contemplated that embodiments of the present disclosure may reduce human error as well.
• In some embodiments, visualization devices, such as magnifiers, may be provided with, attached to, or otherwise disposed on, delivery devices, in order to help enhance visibility of dose measurement markers on the devices. It is contemplated that aspects of one embodiment (such as magnifiers, sleeves, guiding pins, channels, screw and gear mechanisms, rotating parts, threaded parts, grips, springs, etc.) may be combined with aspects of one or more other embodiments, to create various combinations and permutations of features in a single device.
• In some embodiments, devices according to the present disclosure may be depicted as including one type of plunger rod and plunger, or as including a general schematic representation of a plunger rod and plunger. For example, some devices according to the present disclosure may be depicted or described as including, e.g., a plunger rod having a threaded end, which engages with threads on an interior of a plunger such that the plunger rod and the plunger may be screwed together. It is contemplated that multiple and/or different configurations of plunger rods and plungers may be appropriate for each of the embodiments disclosed herein. For example, in some cases, the aforementioned threaded plunger rod and plunger may be used with embodiments disclosed herein. In some embodiments, a plunger rod may not be affixed to a plunger, and instead may be disposed near, next to, or flush against a plunger such that pressure from the plunger rod towards the plunger may push the plunger, but withdrawal, twisting, or other movement of the plunger rod may not cause the plunger to likewise be withdrawn, twisted, or otherwise moved. As another example, in some embodiments, a plunger rod may be affixed to a plunger by an adhesive, or may be of a single piece with a plunger (e.g., may have been manufactured in a single mold with a plunger).
• In some embodiments, devices according to the present disclosure may include various cosmetic features relevant to intended users of the devices. For example, devices according to the present disclosure may be manufactured and sold for use by pediatric patients. In such cases, devices according to the present disclosure may include child-friendly coloring, cartoon images, or other cosmetic features to appeal to children. In some cases, devices according to the present disclosure may include lettering, labeling, or other features designed to be easily recognized by the intended users. For example, lettering on a pediatric device or a device for use by a disabled person or an elderly person may have larger, more accessible labeling so that it may be more easily recognized and read by the user(s) of the device.
• FIG. 1 depicts asyringe10 containing a volume ofdrug product12 and having a dose expel control mechanism. The dose expel control mechanism may include arack2 and apinion3.Rack2 may be formed on an inner surface of a plunger rod1 ofsyringe10 or may be otherwise attached to an inner surface of plunger rod1. In some embodiments,rack2 may, e.g., be engraved, machined, or molded onto plunger rod1.Rack2 may include a plurality of teeth extending along its length.
• Pinion3 may also include a plurality of teeth that are configured to engage with the teeth ofrack2.Pinion3 may be operably connected to an actuator (e.g., a dial or a knob) located external to plunger rod1 via apinion rod4. For example, as shown inFIG. 1, rotation of adial5 may cause rotation ofpinion rod4 and thus rotation ofpinion3. Thus,pinion rod4 may extend from an interior region of syringe10 (where it connects to pinion3) to an exterior region of syringe10 (where it connects to dial5). In the embodiment ofFIG. 1,pinion rod4 may extend partially or fully through a finger flange7 (e.g., on, integral to, or affixed to syringe10). In other embodiments,pinion rod4 may extend through a body wall of plunger rod1 and/orsyringe barrel9 ofsyringe10.Pinion rod4 may be supported by a gasket or seal, such as an O-ring6, where it exits finger flange7 (or, if appropriate, syringe barrel9). O-ring6 may provide physical support to pinionrod4 and/orpinion3 whilepinion3 is in motion and/or at rest. While O-ring6 is described as providing structural support to pinionrod4 and/orpinion3, it is also contemplated that O-ring6 may simply seal the internal region of plunger rod1 from an external region, or both. Additionally, other seals or gaskets, or combinations thereof, may be used instead of, or in addition to, O-ring6, and these seals or gaskets may or may not provide structural support and/or sealing. For example, such seals or gaskets may simply provide a barrier protecting the interior region of syringe from an exterior region or may provide structural support and may also act as a barrier.
• Teeth ofpinion3 may engage with teeth ofrack2 such that, upon rotation ofpinion3 viadial5, the rotational motion ofpinion3 may cause translational motion of plunger rod1. Thus, rotatingpinion3 may cause plunger rod1 to move distally and/or proximally insyringe barrel9, which may also move piston8 (e.g., a stopper) withinsyringe barrel9. By rotation ofdial5, piston8 (which may also act as a stopper) withinsyringe barrel9 may be gradually moved towards the needle end ofsyringe10, so that air and excess drug may be pushed out throughneedle13, primingneedle13 for injection of an appropriate dose ofdrug product12.
• Pinion3 andrack2 may be sized and configured such that rotation ofpinion3 in a given direction or by a given amount (e.g., one clockwise rotation) may causerack2 andpinion3 to disengage from one another, which may cease the ability ofdial5 to advancepiston8. In some embodiments, oncedial5 has been rotated a predetermined amount in a clockwise or counterclockwise direction,rack2 and/orpinion3 may cease to move. For example,pinion3 may be prevented from moving further as a result of reaching a proximal end ofrack2, as a result of disengaging withrack2, as a result of disengaging withpinion rod4, as a result of abutting against a stopper, or dial5 may only be rotatable for a given amount. Accordingly, rotation ofdial5 and pinion3 a given amount in a given direction may serve to complete priming of the syringe needle.
• In some embodiments, when plunger rod1 has been moved a desired amount (at which point rotation ofdial5 and/orpinion3 may or may not be stopped), a user may pulldial5 outwards away from plunger rod1. Outwards movement ofdial5 may disengage dial5 frompinion rod4 and/or may disengagepinion rod4 frompinion3. In some embodiments,pinion rod4 may extend through an opening in a sidewall of plunger rod1, and pullingdial5 outwards may retractpinion rod4 out of the opening so thatpinion rod4 no longer prohibits movement of plunger rod1. In some embodiments, pulling outdial5 may lock it in place, thereby preventing further movement of plunger rod1 via use ofdial5. In some embodiments, pullingdial5 outwards may unlock the outer plunger rod, allowing it to move freely, whether or not movement ofdial5 is locked. In some embodiments, pullingdial5 and/orpinion rod4 outward may disengagepinion3 fromrack2. In some embodiments, a user may not be able to depress plunger rod1 untilpinion3 reaches its terminal position and/or untildial5 is pulled outwards.
• Dial5 may be the only mechanism capable of moving plunger rod1 untilsyringe10 has been primed. For example, the complementary teeth ofrack2 andpinion3 may prevent a user from depressing plunger rod1 (and/or pulling plunger rod1 proximally) untilpinion3 has disengaged fromrack2. This may prohibitdrug product12 from being dispensed untilsyringe10 has been primed and may inhibit under- or over-priming ofsyringe10 and promote accurate dispensation ofdrug product12.
• As shown in the embodiment ofFIG. 1,syringe10 may optionally include amagnifier11 attached to or embedded onsyringe barrel9.Magnifier11 may aid in reading measurement indicators onsyringe barrel9, may aid in observing the presence or absence of air bubbles insyringe barrel9, and/or may aid in determining whether a complete dose ofdrug product12 has been dispensed fromsyringe10.Magnifier11 may be included in a distal region ofsyringe10 and may be any suitable shape or size. For example,magnifier11 may have a circular or rectangular shape or may wrap around all of or a portion of the circumference ofsyringe barrel9. In other embodiments, nomagnifier11 may be included.
• The embodiment depicted inFIG. 1 may be operated in the following manner.Dial5 may be rotated a given amount in a given direction until rotation ofpinion3 stops. A user may detect whetherpinion3 has stopped whendial5 is unable to rotate further and/or when movement of plunger rod1 ceases. As discussed above,pinion3 may stop moving, e.g., as a result of reaching an end region ofrack2, as a result of disengaging withrack2, as a result of disengaging withpinion rod4, as a result of abutting against a stopper, or becausedial5 may only be rotatable for a given amount. Alternatively or additionally, in some embodiments, dial5 may be pulled outwards by a user to prevent further movement of plunger rod1 viadial5.
• Once movement of plunger rod1 viadial5 is complete, a user may optionally confirm the dose level of drug product insyringe barrel9 and/or may optionally confirm whether any air is trapped withinsyringe barrel9. A proximal end of plunger rod1 may then be pushed to inject a dose of drug product.
• FIG. 2 depicts an exemplary variation on thepinion3 depicted inFIG. 1.Pinion20 ofFIG. 2 may include an internal ratchet and pawl mechanism to allow rotation ofpinion20 in a first direction and to prevent rotation ofpinion20 in a second direction, opposite the first direction. For example, only clockwise rotation may be allowed and counterclockwise rotation may be blocked, or vice versa. In some embodiments,pinion20 may be prevented from rotating in a direction that would cause plunger rod1 to move proximally away from the needle end ofsyringe10, while rotation in a direction that would cause plunger rod1 to move distally towards the needle end ofsyringe10 is allowed.
• As shown inFIG. 2, ratchet23 may be coaxial withpinion20, and dial5 (FIG. 1) may be connected to ratchet23, for example, via a pinion rod (such aspinion rod4 depicted inFIG. 1) through acenter25 ofratchet23.Ratchet23 may includeangled teeth24. An interior region ofpinion20 may include a spring-loadedpawl22 operably coupled to the interior region.Pawl22 may be positioned at an angle complementary to the angles ofratchet teeth24 and close enough so that a free end ofpawl22 engagesratchet teeth24. Eachratchet tooth24 may include a rounded surface, over which the free end of eachpawl22 can slide, and a projecting face against which the free end of eachpawl22 may engage and be stopped. Rotation ofdial5 ofFIG. 1 in one direction (e.g., a direction that would cause plunger rod1 to move away from the needle end of syringe10) may cause rotation ofratchet23 such that ratchetteeth24 do not engagepawls22, and ratchet23 may rotate independently ofpinion20. Rotation ofdial5 in the opposite direction, however, may cause ratchet23 to engage withpawls22 and to rotatepinion20 such that plunger rod1 andpiston8 may move distally towards the needle end of the device, allowing for priming ofneedle13 and expulsion of air.
• FIGS. 3A and 3B depict another variation of thepinion3 depicted inFIG. 1. In this embodiment, plunger rod30 may include arack32 extending along at least a portion of its length.Rack32 may include a plurality of teeth34 configured to engage withteeth36 onpinion33. In addition toteeth36,pinion33 may include a stopper tooth in the form ofprotrusion35.Protrusion35 may extend radially further out frompinion33 thanteeth36 and may have a height that is greater than a height ofteeth36.Pinion33 may rotate along rack32 (FIG. 3A) untilprotrusion35 onpinion33 contacts rack32 or plunger rod30 (FIG. 3B), halting rotation ofpinion33. In this way,protrusion35 may prevent more than one rotation ofpinion33. Halting rotation ofpinion33 may consequently halt advancement of plunger rod30 andpiston38 beyond a predetermined point. The predetermined point may correspond to, e.g., a point at which excess air and dosage of a drug product may be expelled from syringe10 (seeFIG. 1), resulting in accurate priming ofsyringe10. In some embodiments, whenprotrusion35 contacts plunger rod30 andpinion33 assumes the position shown inFIG. 3B,protrusion35 may be free ofrack32, and plunger rod30 may slide freely against it. Accordingly, in the embodiment ofFIGS. 3A and 3B, instead of the rack length controlling the amount of movement of plunger rod30 is allotted to prime the syringe, the circumference ofpinion33 may control this movement.
• The physical cessation of further pinion movement caused byprotrusion35 onpinion33 may also provide tactile feedback to a user to indicate that a proper dose has been set and thatsyringe10 has been primed. Inclusion ofprotrusion35 onpinion33 may additionally prevent over- or under-rotation ofpinion33 in an undesirable direction (e.g., that would allow movement of plunger rod in a proximal direction).Protrusion35 may be useful to prevent overfilling ofsyringe10 or intake of air intosyringe10 during handling, packaging, storage, and/or transport. In further embodiments, aprotrusion35 may be located onrack32 instead of, or in addition to, pinion33 to control movement ofpinion33.
• FIGS. 3C and 3D depict another variation of plunger rod1 depicted inFIG. 1.Plunger rod40 ofFIGS. 3C and 3D may include a locking mechanism configured to prevent accidental depression ofpiston48, e.g., when the syringe is being packaged, stored, handled, and/or filled. In some embodiments,plunger rod40 may include a telescoping inner portion49 (e.g., an inner tubular portion or a column) having arack42.Inner portion49 ofplunger rod40 may includepiston48 connected to a distal end thereof.Inner portion49 may move relative to a stationary outer portion41 (e.g., an outer lumen). Rotation ofdial45 may extendinner portion49 distally out fromouter portion41 so thatinner portion49 moves independently fromouter portion41.
• Dial45 may be operably connected to the telescopinginner portion49 by pinion rod44 (e.g., a shaft) andpinion43. Rotation ofdial45 may in turn rotatepiston rod44 andpinion43. Teeth onpinion43 may engage with teeth onrack42 ofinner portion49, movinginner portion49 distally out fromouter portion41.FIG. 3C depictsinner portion49 oftelescoping plunger rod40 retracted withinouter portion41, andFIG. 3D depictsinner portion49 oftelescoping plunger rod40 extending out fromouter portion41. Turningdial45 may thus movepiston48 distally towards the needle end of the syringe to prime the needle and remove air bubbles.
• Whileinner portion49 ofplunger rod40 may extend fromouter portion41 during priming of the needle,outer portion41 may not move during dose preparation. In such an exemplary embodiment, dial45 and/orpinion rod44 may optionally interfere withouter portion41 ofplunger rod40 so thatplunger rod40 can't move relative to the syringe barrel and can't be depressed by pressing onthumbpad47 ofplunger rod40 during dose preparation. For example, to connectpinion43 to dial45,pinion rod44 may extend through an opening of telescopingouter portion41 ofplunger rod40. Thus, whenpinion rod44 is connected to pinion43, extension ofpinion rod44 through a sidewall ofouter portion41 may prevent movement ofouter portion41. Becauseouter portion41 cannot be moved, plunger rod may not be able to be depressed. Pulling outdial45 may disengagepinion rod44 frompinion43, so thatpinion rod44 no longer extends throughouter portion41. As a result, oncedial45 is pulled out,pinion rod44 may be removed from engagement with the telescoping portions and may no longer extend through the telescoping portions, allowingplunger rod40 may to move freely within the syringe barrel. Movement ofplunger rod40 in a distal direction by pressingthumbpad47 may allow for administration of the dose.
• In the embodiment ofFIGS. 3C and 3D, when thumbpad47 is depressed, telescopinginner portion49 ofplunger rod40 may be fixed in place relative toouter portion41 so that depressingthumbpad47 and movingplunger rod40 does not cause telescopinginner portion49 to collapse back withinouter portion41.Outer portion41 andinner portion49 ofplunger rod40 may, for example, be coupled to each other with positive locking teeth (e.g.,teeth46 of outer portion41), which may allowinner portion49 to extend distally fromouter portion41 but may prohibit backwards movement ofinner portion49 intoouter portion41. This may prevent the two telescoping portions from collapsing one into the other when thumbpad47 is depressed andplunger rod40 moves distally to expel the dose. This may also prevent proximal movement ofinner portion49 during priming.
• In use, dial45 may be rotated to prime a syringe as depicted inFIGS. 3C and 3D and may allow for finer and/or more controlled movements ofplunger rod40 for such priming. As described above, the inclusion ofdial45 may prevent discharge of any product volume intended for dosage until priming is complete and, e.g., dial45 has been pulled outwards to unlock movement ofplunger rod40. Although one type of locking mechanism associated withdial45 is described, it is contemplated that any suitable type of locking mechanism may be incorporated, and that such a locking mechanism may be activated and/or deactivated by pulling, depressing, sliding, or otherwise manipulatingdial45.
• For example, other variations of a locking mechanism are depicted in cross section inFIGS. 4A and 4B. The locking mechanisms ofFIGS. 4A and 4B may be used instead of, or in addition to, dial45 ofFIGS. 3C and 3D. In the embodiment ofFIG. 4A, the entirety ofplunger rod50 or a proximal region of plunger rod50 (e.g., a telescoping outer portion of the plunger rod) may include a physical stop (e.g., an interfering bump or projection) to prevent depression ofplunger rod50 during dose preparation and priming—or to allow only enough depression to prepare and prime the dose. In the embodiment ofFIG. 4A, an interfering projection51 (shown in top-down cross-section) may preventplunger rod50 from moving distally untilplunger rod50 and/or the portion ofplunger rod50 havingprojection51 is rotated relative to other portions of the syringe, e.g., a finger flange (not shown), astopper53 located at a mouth of asyringe barrel58, and/orsyringe barrel58. In the embodiment ofFIG. 4B,plunger rod50 as a whole may have a cross-sectional shape that is not radially symmetrical, such that the shape ofplunger rod50 may prevent it from moving distally untilplunger rod50 is rotated relative to other portions of the syringe, e.g., a finger flange,stopper53, and/orsyringe barrel58. In order to depressplunger rod50,plunger rod50,stopper53, and/orbarrel58 may be rotated relative to other portions of the syringe in order to be able to depressplunger rod50 enough to fully dispense the drug dose.
• In some embodiments,plunger rod50 may not be capable of moving past, e.g., a finger flange orstopper53 in the syringe barrel untilplunger rod50 is rotated a certain number of degrees (e.g., 90 degrees) in relation to the finger flange or the stopper. In some embodiments, the finger flange orstopper53 may be rotated (e.g., 90 degrees) in relation toplunger rod50. For example,plunger rod50 may have a particular cross-sectional shape (e.g., a generally rectangular shape and/or projections51), andsyringe barrel58 and/orstopper53 may include a blocking component and/or may be sized and shaped so thatprojections51 ofplunger rod50 cannot fit through until the relevant parts have been rotated sufficiently so that the complementary shapes align andplunger rod50 can pass through.
• In some embodiments, anopening52 instopper53 and/or syringe barrel58 (and/or a finger flange, not shown), and a cross-section ofplunger rod50 may have complementary shapes but may be offset from each other unless one or the other is rotated until the shapes align. InFIGS. 4A and 4B,projections51, or the general shape ofplunger rod50, do not align withopening52 until the finger flange orplunger rod50 is rotated sufficiently. While twoprojections51 fromplunger rod50 and a corresponding shape of opening52 are depicted inFIG. 4A, and while a given cross-sectional shape ofplunger rod50 is depicted inFIG. 4B, it is contemplated that any suitable number, size, and shaped openings and projections and/or cross-sectional shapes may be used. Additionally, while the exemplary embodiments show the required rotation as being 90 degrees, it is contemplated that any suitable amount of rotation (less than or greater than) 90 degrees may be needed.
• FIGS. 4C-4E depict a side view of a syringe54 havingplunger rod50, withprojections51, in three different positions. Syringe54 may includestopper53, through whichprojections51 cannot fit untilprojections51 andstopper53 have been rotated relative to one another such that the shape ofprojections51 fits a complementary opening in stopper53 (see, e.g., dotted lines inFIG. 4A).Plunger rod50 may be coupled to aplunger56, which may be configured to fit snugly within abarrel58 of syringe54. Syringe54 may include a volume of adrug product12 suitable for dispensing from syringe54. InFIG. 4C, syringe54 is depicted in a first, un-actuated position.Projections51 are positioned aboutplunger rod50 in a first orientation. InFIG. 4D, syringe54 is depicted in a second, partially actuated position.Projections51 in the first orientation are blocked from passing throughstopper53, and thus the further depression ofplunger rod50 is also blocked. InFIG. 4E, syringe54 is depicted in a fully actuated position. Upon rotation of plunger rod50 (e.g., in the manner indicated by the curved arrow, or alternately in the opposite direction),projections51 may be moved into a second orientation aboutplunger rod50. In the second orientation,projections51 may pass throughstopper53, allowing for further depression ofplunger rod50 andplunger56.
• In some embodiments,projections51 may be positioned onplunger rod50 such that they do not protrude from the general profile of syringe54. For example,projections51 may be located inside, e.g.,barrel58 before syringe54 is actuated (e.g., inFIG. 4C). In such embodiments,projections51 may be located, e.g., inside a portion ofstopper53 before syringe54 is actuated. In some such embodiments,stopper53 may have a greater thickness so as to accommodateprojections51, and may have a proximal cavity sized and configured to houseprojections51 in a first orientation, and a more distal cavity configured to accommodateprojections51 in a second orientation, such that rotation ofplunger rod50 and/orprojections51 may allow for movement ofplunger rod50 in a distal direction.
• In some embodiments, a second set of projections may be incorporated inplunger rod50 either proximally or distally fromprojections51. The second set of projections may have similar geometry toprojections51, but may be radially offset fromprojections51, such that additional rotation ofplunger rod50 is required for the second set of projections to pass through an opening in, e.g., stopper53 (e.g., opening52). Alternately, a second set of projections may have a geometry that cannot fit through an opening, such thatplunger rod50 is inhibited from moving in a given direction by their geometry. Such a second set of projections may be useful in, e.g., limiting movement ofplunger rod50 either before or afterprojections51 have passed through the opening. In some embodiments, limiting of movement in this manner may be used in controlling an amount of movement ofplunger rod50 allowed for primingsyringe10, prior to further rotation ofplunger rod50 to allow for dispensing a dosage amount fromsyringe10. In further embodiments, limiting of movement in this manner may be used to control a dosage volume that may be dispensed fromsyringe50. See, for example,FIGS. 15A-E described further below. As is the case with all embodiments depicted and described herein, this embodiment may be combined with aspects of other embodiments described herein.
• In some embodiments, the syringe may be configured to provide feedback to the user to indicate when rotation ofplunger rod50 andprojections51 and/or the finger flange is complete andplunger rod50 is aligned with openings52 (seeFIGS. 4A-4B). For example, a “clicking” noise or other audio or tactile feedback mechanism may be incorporated into the syringe.
• Referring now toFIG. 5, anotherexemplary syringe60 is pictured having a dose expel control mechanism. In the embodiment ofFIG. 5, the dose expel control mechanism includes two sets of angled helical threads. A first set ofhelical threads62 is included on an exterior surface ofplunger rod61.Threads62 may extend around the entire circumference ofplunger rod61 or around a portion of the circumference. A second set ofhelical threads63, complementary to externalhelical threads62 ofplunger rod61, are included on an internal circumference ofsyringe barrel69 and/orfinger flange64 through whichplunger rod61 passes.Threads62 may extend around the entire circumference ofsyringe barrel69 and/orfinger flange64 or around a portion of the circumference.Threads62,63 may be engraved, molded, machined, attached, or otherwise included to the surfaces ofplunger rod61 andsyringe barrel69 orfinger flange64, respectively.
• Plunger rod61 may be rotated to movethreads62 ofplunger rod61 throughthreads63, converting the twisting motion ofplunger rod61 into translational (or linear) motion of plunger rod61 (and thus, piston68) insyringe barrel69. The linear motion ofpiston68 may push air bubbles and excess drug out throughsyringe needle66. Thus,needle66 may be primed and readied for injection by twisting ofplunger rod61. Boththreads62,63 may be sized and configured such that, oncethreads62 are moved entirely throughthreads63, air is removed from withinsyringe barrel69, and a predetermined volume of drug product is expelled fromsyringe needle66 toprime needle66.
• Threads62,63 may also preventplunger rod61 from being depressed before priming ofneedle66 occurs. For example, in order to depressplunger rod61 to dispense the drug product,plunger rod61 must first be twisted—i.e.,needle66 must first be primed. Oncethreads62 are rotated throughthreads63 and priming is complete, a user may be able to depressplunger rod61 to deliver the dosage.
• As discussed above in relation toFIG. 1, the embodiment ofFIG. 5 may also optionally include amagnifier65.Magnifier65 may aid in reading magnified volume measurements of the drug product insyringe barrel69, may aid in observing the presence or absence of air bubbles insyringe barrel69, and/or may aid in determining whether a complete dose of drug product has been dispensed fromsyringe60.Magnifier65 may be included in a distal region ofsyringe60 and may be any suitable shape or size. For example,magnifier65 may have a circular or rectangular shape or may wrap around all of or a portion of the circumference ofsyringe barrel69. In other embodiments, nomagnifier65 may be included.
• To operatesyringe60, a user may first rotateplunger rod61.Plunger rod61 may need to be rotated a partial rotation, one complete rotation, or more than one complete rotation in order to passthreads62 throughthreads63 and disengagethreads62 fromthreads63. At this time, a user may optionally confirm the dose level insyringe barrel69. The user may usemagnifier65 to perform this step, ifmagnifier65 is included. The user may then pushplunger rod61 to dispense the dose of drug product.
• In some embodiments,syringe60 may provide feedback to the user to indicate when rotation ofplunger rod61 is complete and the dose is ready for injection. For example, a “clicking” noise or other audio or tactile feedback mechanism may be incorporated intosyringe60.
• The embodiment ofFIGS. 6A-6E may operate in a similar manner to the embodiment ofFIG. 5, but may further include a locking mechanism to prevent accidental depression ofplunger rod71 when priming of the needle is complete. For example, likeFIG. 5, the embodiment ofFIGS. 6A-6E includesthreads72 onplunger rod71, which must be twisted throughcorresponding threads73 ofsyringe barrel75. However,plunger rod71 may also include astop74 located on an outer surface ofplunger rod71, proximal tothreads72.
• Stop74 may be sized and shaped to fit within aslot76 extending throughthreads73. For example, stop74 may enter a vertical portion ofslot76 passing through some ofinternal threads73 of syringe barrel75 (depicted in, e.g., section A-A inFIGS. 6B and 6C).Slot76 may also include a horizontal section (e.g., along section B-B depicted inFIGS. 6B and 6D). Once stop74 slides fully into the vertical section ofslot76, the user must rotateplunger rod71 in the direction opposite the direction ofthreads72 ofplunger rod71 in order to slidestop74 through the horizontal portion ofslot76 and to advanceplunger rod71 further distally. Because of the need for an opposing direction of rotation, the risk of accidental advancement ofplunger rod71 may be reduced. Finally, the plunger may be depressed downwards to movestop74 through a second vertical section of slot76 (e.g., section C-C depicted inFIGS. 6B and 6E), to expel a volume of the drug product.
• Slot76 may be shaped to require clockwise or counterclockwise rotation, depending on the relative locations of the horizontal and vertical sections. Additionally, althoughslot76 is shown and described as including one horizontal portion requiring rotation ofrod71, it is contemplated that multiple horizontal portions may be included, requiringrod71 to be rotated addition times in the same direction or in multiple directions. Further, although stop74 is depicted as including two projections onplunger rod71, it is contemplated that one projection or more than two projections may be included as part ofstop74, andslot76 may be shaped and sized to accommodate the different configurations ofstop74.
• Althoughthreads73 are described as being on an internal surface ofsyringe barrel75, it is contemplated thatthreads73 andslot76 may be located on an internal surface of a finger flange instead of, or in addition to,syringe barrel75. Moreover, as is the case with all embodiments depicted and described herein, the above-described embodiment may be combined with aspects of other embodiments described herein. For example,rod71 may include additional projections and/or geometries, such as those shown inFIGS. 4A-4E andFIGS. 15A-15E, to provide a hard stop to the movement ofrod71.
• Referring now toFIGS. 7A and 7B, another embodiment of a dose expel control mechanism is depicted. InFIG. 7A,syringe80 includes complementaryhelical threads82 and83.External threads82 in this embodiment are located on asleeve87 surroundingplunger rod81 instead of directly onplunger rod81. A close-up of the threaded portions ofsyringe80 is depicted inFIG. 7B.Sleeve87 may allow for free distal movement of plunger rod81 (towards the needle end of syringe80), but may block undesirable proximal movement of piston88. Before depression ofplunger rod81, rotation of sleeve87 (e.g., via twisting ofdial rod85 located at a proximal end of sleeve87) may be transformed into a controlled sliding movement ofsleeve87 intosyringe barrel89 viathreads82 onsleeve87 and corresponding threads onfinger flange84 and/orsyringe barrel89. The controlled sliding movement ofsleeve87 may gradually pushplunger rod81 and stopper88 towards the distal needle end of the device. Movement ofplunger rod81 through the threaded region may allow for controlled expulsion of air and priming ofneedle86.
• As in previous embodiments, the embodiment ofFIG. 7A may also optionally include amagnifier90.Magnifier90 may magnify volume measurements of the drug product insyringe barrel89, may aid in observing the presence or absence of air bubbles insyringe barrel89, and/or may aid in determining whether a complete dose of drug product has been dispensed fromsyringe80.Magnifier90 may be included in a distal region ofsyringe80 and may be any suitable shape or size. For example,magnifier90 may have a circular or rectangular shape or may wrap around all of or a portion of the circumference ofsyringe barrel89. In other embodiments, nomagnifier90 may be included.
• To operatesyringe80,dial rod85 may be rotated a partial rotation, one complete rotation, or more than one complete rotation in order to passthreads82 ofsleeve87 throughthreads83 untilthreads82 are disengaged fromthreads63. At this time, a user may optionally confirm the dose level insyringe barrel89. The user may usemagnifier90 to perform this step, ifmagnifier90 is included. The user may then pushplunger rod81 to dispense the dose of drug product.
• In some embodiments,syringe80 may provide feedback to the user to indicate when rotation ofplunger rod81 is complete and the dose is ready for injection. For example, a “clicking” noise or other audio or tactile feedback mechanism may be incorporated intosyringe80. In some embodiments, a user may know that priming is complete becausedial rod85 may not rotate any further,plunger rod81 may not move any further when twisting, and/or dialrod85 may abut a portion offinger flange84 and/orsyringe barrel89, preventing further distal movement ofdial rod85.
• In some embodiments, a locking mechanism like the one discussed above in reference toFIGS. 6A-6E may be incorporated intoplunger rod81. By requiring thatplunger rod81 be turned (e.g., 90 degrees, although turningplunger rod81 more or less is than 90 degrees is also contemplated) prior to administration to allowplunger rod81 to move freely,plunger rod81 may be prevented from being pressed in a distal direction during needle priming.
• In further embodiments, a locking or stopping mechanism may be incorporated intosleeve87 ofFIGS. 7A and 7B. Such a mechanism is depicted inFIG. 8. By incorporatingstops91 and/or92 (e.g., tabs or projections) onto sleeve87 (e.g., at positions above and/or belowthreads82 onsleeve87 andthreads83 in the syringe barrel), over-rotation of the sleeve in either direction (and thus over-priming or unwanted removal of sleeve87) may be prevented.Stop91 may be located proximal ofthreads82 and may be configured to stop movement ofsleeve87 towards the distal end region of the syringe barrel.Stop92 may be located distally fromthreads82 and may be configured to stop movement ofsleeve87 towards the proximal end region of the syringe barrel.
• Referring now toFIGS. 9A-9D, anothersyringe100 is pictured with a further embodiment of a dose expel control mechanism. This embodiment may include, for example, a key103 to act as a removable stop at a junction betweensyringe barrel109 andplunger rod101.Key103 may obstruct movement ofplunger rod101 when it is in place betweensyringe barrel109 and a proximal region ofplunger rod101.Key103 may be placed betweenplunger rod101 andsyringe barrel109, e.g., during packaging, filling, or preparation ofsyringe100.Key103 may snap-fit, friction-fit, twist-fit, or otherwise be set in place in any suitable manner. A user may then remove key103 just prior to use ofsyringe101. To remove key103, a user may pull a tab included onkey103, may snap off a tab, may break a frangible portion, may twist key103, or may remove key103 in any suitable manner.Syringe100 is depicted as having amagnifier105 disposed at a distal end portion ofsyringe barrel109, which may assist in, e.g., visualizing a level of product inbarrel109.
• It is contemplated that the key and/or locking mechanisms described above may be useful in the context of fillable syringes as well as pre-filled syringes, which may undergo sterilization, packaging, storage, and/or shipment after being filled. In pre-filled syringes, key103 may prevent the accidental depression ofplunger rod101 prior to its intended use, thus preserving the sterility, safety, and dose volume of the drug product. Variations ofkey103 may include, for example, a frangible stop that may be broken by applying a certain amount of force toplunger rod101.
• In addition tokey103, the embodiment depicted inFIG. 9A may include a locking mechanism similar to that discussed with respect to, e.g.,FIGS. 4A-4E, above, orFIGS. 15A-E, described further herein. For example, as is shown inFIG. 9D, aslot107 may be included in astopper104 ofsyringe100.Stopper104 may have anopen portion110 through whichplunger rod101 may move without being rotated to a set position. Theopen portion110 may allow the plunger to move a distance suitable for primingneedle106.Slot107 may be sized and shaped to fit the cross-sectional area ofplunger rod101 in a particular orientation. For example,plunger rod101 may include aflange102 sized and shaped to pass throughslot107 when aligned withslot107.Stopper104 may be disposed at a proximal region ofsyringe barrel109, such thatplunger rod101 must be rotated to a set position to alignflange102 withslot107 prior to being depressed through at least part ofstopper104. Althoughflange102 andcorresponding slot107 are depicted,slot107 andplunger rod101 may have any suitable complementary cross-sectional shapes. Moreover,plunger rod101 may have multiple cross-sectional geometries along its length, to either provide a hard stop to distal movement ofplunger rod101 or require additional turning ofplunger rod101 relative tostopper104 to further move plunger rod101 (see, e.g.,FIGS. 15A-15E). As is the case with all embodiments depicted and described herein, this embodiment may be combined with aspects of other embodiments described herein.
• Oncekey103 is removed,plunger rod101 may be allowed to move distally from its original position down throughopen portion110 ofstopper104. This distal movement ofplunger rod101 may movepiston108 just enough toprime needle106 and to remove any air bubbles.Stopper104 may halt additional distal movement ofplunger rod101 when flange102 hits the inner portion ofstopper104, whereslot107 begins. At that time,plunger rod101 may need to be rotated to alignflange102 withslot107 instopper104 beforerod101 can be pushed distally through the rest ofstopper104 to movepiston108 and discharge the drug dose.
• In some embodiments,syringe100 may be configured to provide feedback to the user to indicate whenplunger rod101 andflange102 are aligned withslot107 and/or when priming ofsyringe100 is complete. For example, a “clicking” noise or other audio or tactile feedback mechanism may be incorporated intosyringe100.
• Referring now toFIGS. 10A-10C, a cross-sectional image of asyringe200 is depicted, with various embodiments of a further dose expel control mechanism.Syringe200 may include abarrel240 and aplunger rod220.Plunger rod220 may be coupled to afirst plunger222, which may be configured to fit into an opening in aflange210 positioned at a proximal plunger rod end ofbarrel240.Flange210 may be configured to fit securely withinbarrel240, and may be, e.g., sealed against an interior ofbarrel240 with an O-ring208. The interior ofbarrel240 may include asecond plunger260 configured to fit snugly within the interior ofbarrel240. Afirst fluid244 may be disposed insidebarrel240 to a proximal side ofplunger260, and a second fluid, e.g., adrug product212, may be disposed insidebarrel240 to a distal side ofplunger260. A needle, cannula, tube, or other attachment may be coupled to a distal end ofbarrel240, through which a fluid, e.g.,drug product212, may be expelled or withdrawn.
• The opening offlange210 may have a cross-sectional width a into whichplunger222 may be configured to securely fit. In some embodiments,plunger222 may be configured to form a seal againstflange210, e.g., with the use of an O-ring224. The portion offlange210 having width a may also have a depth c. As shown inFIG. 10A, in some embodiments depth c may correspond to a distance between a distal side ofplunger222 and a distal side offlange210. Distal movement ofplunger222 for, e.g., a distance corresponding to depth c (e.g., caused by depression ofplunger rod220 towards flange210) may cause a first volume offluid244 in the opening offlange210 to be displaced distally by a distance corresponding to depth c. Displacement of the first volume offluid244 may inturn push plunger260, causing a second volume ofdrug product212 to be expelled fromsyringe200.Barrel240 may have a cross-sectional width b located distally fromflange210, where width b is greater than width a. Due to the differences between widths a and b (and thus the differences in fluid volume capacity in the portions ofsyringe200 having widths a and b), distal movement ofplunger222 by, e.g., a distance corresponding to depth c may causeplunger260 to move distally by a smaller distance d. In this manner, a movement of, e.g.,plunger rod220 in the distal (or proximal) direction may be converted into a proportionally smaller, and thus more controllable, movement ofplunger260 and thus a more controllable expulsion (or withdrawal) of a volume ofdrug product212.
• The embodiments depicted inFIGS. 10B and 10C may differ somewhat from the embodiment ofFIG. 10A. Referring toFIG. 10B, cross-sectional widths a and b may both be widths of an opening inflange210. In such embodiments, asecond plunger rod262 may be disposed within the barrel, such that a portion ofplunger rod262 is disposed within, and extends across an interior of, the portion offlange210 having width b.Plunger rod262 may be coupled to, and may extend proximally from,plunger260. Moreover,plunger rod262 may have a proximal side that extends across the area of the opening inflange210 having width b, such that distal movement offluid244 may cause distal movement ofplunger rod262, which in turn may pushplunger260 distally. Referring toFIG. 10C, cross-sectional width b may refer to the internal cross-sectional width ofbarrel240, as with the embodiment depicted inFIG. 10A, andsecond plunger rod262 may be disposed within, and may extend across an interior of,barrel240. Similarly to the embodiment depicted inFIG. 10B,plunger rod262 may have a proximal side that extends across the internal area ofbarrel240 having width b, such that distal movement offluid244 may cause distal movement ofplunger rod262, which in turn may pushplunger260 distally. As with the embodiment ofsyringe200 depicted inFIG. 10A, a movement of, e.g.,plunger rod220 in the distal direction may be converted into a proportionally smaller, and thus more controllable, movement ofplunger260 and thus a more controllable expulsion of a volume ofdrug product212.
• With respect to the embodiments depicted inFIGS. 10B and 10C,plunger rod262 may form a seal with adjacent parts ofsyringe200, such thatfluid244 may not travel distally through/past plunger rod262. This may result in the need forless fluid244, and may allow for a region of “empty” space betweenfluid244 anddrug product212, which may aid in preventing leakage or mixture offluid244 withdrug product212. The “empty” spacy may include a vacuum, or may include, e.g., dry or sterile air. In some embodiments, the “empty” space may include additional fluid244 (or another fluid) to provide additional structural support to the syringe. In any of the embodiments depicted inFIGS. 10A-10C,fluid244 may be any suitable liquid or gaseous fluid, such as, e.g., water for injection, dry gas, sterile air, or the like.
• Referring now toFIG. 11A, a cross-section of anothersyringe300 is depicted with a further embodiment of a dose expel control mechanism.Syringe300 may include abarrel340, aplunger360, and adrug product312. Aplunger rod320 may extend intobarrel340, and may include several ratchet-type teeth321 that may engage withpinions328, which in turn may engage withratchet type teeth326 on an interior ofbarrel340. Each ofpinions328 may be coupled to one ofrods330, which may be coupled toplunger360. A needle, cannula, tube, or other attachment (not pictured) may be coupled to a distal end ofbarrel340, through which a fluid (e.g., drug product312) may be expelled or withdrawn.
• Movement ofplunger rod320 in the proximal or distal direction may translate, viapinions328 andteeth326, to proportionally smaller movement ofplunger360. In this manner, controlled movement ofplunger360 in the distal direction may, e.g., expeldrug product312 distally at a controlled rate. The sizes and shapes of the teeth, ratchets, and pinions insyringe300 may be selected so as to create a desired controlled speed of movement ofplunger360.
• FIG. 11B depicts, in cross-section, a further embodiment ofsyringe300, in whichteeth321 ofplunger320 may engage withpinions328, which may each be coupled with, and may rotate coaxially and in tandem with, relativelysmaller pinions329, which in turn may engage withteeth326 on the interior ofbarrel340.Pinions328 may pass adjacent toteeth326, such that only pinions329 engage withteeth326. Each ofpinions328,329 may be coupled to one ofrods330, which may be coupled toplunger360.
• Due to the relatively smaller diameter ofpinions329 as compared topinions328, movement ofplunger320 in the proximal or distal direction may translate, viapinions328,pinions329, andteeth326, to proportionally smaller movement ofplunger360. In this manner, controlled movement ofplunger360 in the distal direction may, e.g., translate to relatively smaller movement ofplunger360 and controlled expulsions ofdrug product312 distally. As withFIG. 11A, the sizes and shapes of the teeth, ratchets, and pinions insyringe300 may be selected so as to create a desired controlled speed of movement ofplunger360.
• Although the embodiments depicted inFIGS. 11A and 11B each show a symmetricalarrangement including teeth321 on two sides ofplunger rod321, two ofpinions328, two of pinions329 (with respect to the embodiment ofFIG. 11B), and two ofrods330, a single arrangement, e.g.,teeth321 engaged with onepinion328, which may be coupled to one pinion329 (with respect to the embodiment ofFIG. 11B), which may be coupled to onerod330, is also contemplated. One of ordinary skill in the art will understand that more or fewer pinions, and/or rods may be incorporated into embodiments of the present disclosure, to achieve controlled delivery of the contents ofsyringe300.
• Referring now toFIG. 12, a cross-sectional side view of anothersyringe400 is depicted with a further embodiment of a dose expel control mechanism.Syringe400 may include abarrel402, aninner sleeve404, and aplunger rod406.Plunger rod406 may extend intobarrel402 and into anopening410 defined byinner sleeve404, whereopening410 is narrower than a general inner width ofbarrel402. Opening410 may receive or contain adrug product408.
• Generally,syringe400 may be configured to provide a relatively narrow channel or path (e.g., in opening10) through whichdrug product408 may be pushed byplunger rod406, such that distal movement byplunger rod406 may be translated into relatively gradual and controllable expulsion or delivery ofdrug product408 through a distal end of syringe400 (e.g., via a needle, cannula, tube, or other attachment coupled to syringe400), as compared to a syringe having a relatively wider channel or path fordrug product408.
• As shown, a distal portion ofplunger rod406 may be configured to fit within opening410 ofinner sleeve404.Inner sleeve404 may be of a piece with barrel402 (e.g., may be contiguous with, or may be made in a single mold with, barrel402), or may be a separate piece inserted intobarrel402.Inner sleeve404 may extend partly or fully through an interior ofbarrel402. In some embodiments, as shown,inner sleeve404 may be disposed in a distal portion of the interior ofbarrel402.
• Plunger rod406 may be fitted with, coupled to, or may otherwise contact a plunger configured to enclose a volume ofdrug product408 withinopening410 and/or betweenplunger rod406 and a distal end ofsyringe400.Plunger rod406 and/or a plunger coupled toplunger rod406 may be configured to fit snugly withinbarrel402, so as to containdrug product408 without leakage ofdrug product408 into the general interior of barrel402 (e.g., proximally from inner sleeve404).Opening410 andplunger rod406 may be configured to have relatively narrow widths, thus creating the relatively narrow channel through whichdrug product408 may be expelled fromsyringe400.
• In some embodiments,barrel402 may be marked with measurement indicators, so as to visually indicate a volume of fluid left in, and/or dispensed from,syringe400. Moreover, as shown or described with respect to other embodiments,syringe400 may optionally include a magnifier attached to or embedded onsyringe barrel402, which may aid in reading measurement indicators onsyringe barrel102, may aid in observing the presence or absence of air bubbles insyringe barrel102, and/or may aid in determining whether a complete dose ofdrug product408 has been dispensed fromsyringe400. Such a magnifier may be included in a distal region ofsyringe10 and may be any suitable shape or size. In other embodiments, nomagnifier11 may be included.
• In further embodiments, the narrow channel ofsyringe400 may be achieved in a manner that does not requireinner sleeve400. For example, a syringe barrel (e.g., barrel402) may be manufactured to itself have a relatively narrow interior configured to receiveplunger rod406, such that no narrowing insert need be disposed inside the barrel. The narrow interior of the syringe barrel may be sized and configured to house a volume of a drug product (e.g., drug product408) that will result in a desired or suitable amount of the drug product being dispensed fromsyringe400 upon its use.
• Aspects of the embodiment depicted inFIG. 12 may be particularly suited to being combined with aspects of other embodiments discussed herein. For example, any embodiment of the present disclosure may also incorporate a relatively narrow (or narrowed) interior to allow for more gradual and controlled delivery of a drug product.
• Referring now toFIGS. 13A-13C, cross-sectional side views of anothersyringe420 are depicted, with a further embodiment of a dose expel control mechanism.Syringe420 may include abarrel422, aplunger rod424, and aplunger426. An interior428 ofbarrel422 may house or receive adrug product430 and aninsert432.
• Insert432 may include a compressible portion, such thatinsert432 may be compressed by a predetermined distance or volume. In some embodiments, for example, insert432 may be a spring, such as a wave spring, a coiled spring, or any other spring known in the art. In further embodiments, for example, insert432 may be made from a compressible material, such as rubber, silicone, or plastic. In some embodiments, insert432 may be affixed to, or otherwise held in place within, a particular location/orientation inbarrel422.
• An initial configuration of a filledsyringe420 is depicted inFIG. 13A. In this configuration, a quantity ofdrug product430 is located between plunger246 and insert432, as is an empty space (e.g., an air bubble) ininterior428. As depicted inFIG. 13B, whenplunger rod424 is depressed distally, the quantity ofdrug product430 betweenplunger426 and insert432 may be expelled distally fromsyringe420, along with the air bubble (e.g., via a needle, cannula, tube, or other attachment coupled to a distal end of syringe420). Upon contactingplunger426, insert432 may offer some resistance against further distal movement of426. This may provide, e.g., a tactile, auditory, and/or visual feedback to a user ofsyringe420 indicating thatsyringe420 is primed and the air bubbles have been removed.
• A distance a by which insert432 may be compressed may be proportional to a volume ofdrug product430 suitable for a dosage contained withinbarrel422. For example, in some embodiments, a volume defined byinsert432 may correspond to a volume ofdrug product430 suitable for a dosage contained withinbarrel422. Thus, as shown inFIG. 13C, whenplunger426 is moved further distally so as to compressinsert432 by distance a, a quantity ofdrug product430 suitable for a dosage may be dispensed from the distal end ofsyringe420. For example,plunger426 may be moved distally so that a volume ofdrug product430 corresponding to the volume defined byinsert432 is dispensed.Insert432 may be configured to prevent its compression or movement beyond distance a, thus ensuring that only a quantity ofdrug product430 suitable for dosage is dispensed. A leftover quantity ofdrug product430 may remaininside barrel422 after a dosage amount is dispensed. In some cases, this may allow for increased dosage accuracy, asplunger426 need not interact with any tapering of the diameter ofbarrel422 that may occur near a distal end portion ofsyringe420.
• Referring now toFIGS. 14A-14C, cross-sectional side views of anothersyringe440 with a further embodiment of a dose expel control mechanism are depicted in three stages.Syringe440 may include abarrel442, a plunger having anouter plunger rod444 and aninner plunger rod446, both of which may be actuated by a knob ordepressor448.Inner plunger rod446 may be disposed inside, and coaxially with,outer plunger rod444. Inner plunger rod may protrude proximally and/or distally fromouter plunger rod444. Aplunger450 may be coupled to either or both ofinner plunger rod446 andouter plunger rod444. Specifically,plunger450 may be movably coupled toinner plunger rod446. A volume ofdrug product454 may be received or housed withinbarrel442 betweenplunger450 and a distal end ofsyringe440. Aninsert456 may be disposed distally fromplunger450, e.g., at a distal end portion of the interior ofbarrel442.Insert456 may include achannel458, sized and configured to accommodate inner plunger rod446 (but not plunger450 or outer plunger rod444).
• As shown inFIG. 14A,inner plunger rod446 may protrude both proximally and distally fromouter plunger rod444. A seal (not shown) may exist betweeninner plunger rod446 andouter plunger rod444, to prevent leakage of any fluid between the plunger rods. In some embodiments,inner plunger rod446 may only protrude distally or may only protrude proximally fromouter plunger rod444. For example,inner plunger rod446 may be a telescoping plunger rod, which may be configured to extend only distally fromouter plunger rod444. In some embodiments,inner plunger rod446 may be configured to optionally telescope, slide, or otherwise move throughouter plunger rod444 andplunger450. In some embodiments, for example,inner plunger rod446 may include a threaded portion on its exterior (not shown), configured to mate with complementary threads on an interior of outer plunger rod444 (not shown). Wheninner plunger rod446 andouter plunger rod444 are engaged via these threads or by any other mechanism,inner plunger rod446 andouter plunger rod444 may move proximally and distally withinbarrel442 in tandem. Upon rotation of inner plunger rod446 (e.g., by turning knob or depressor448) relative toouter plunger rod444,inner plunger rod446 may be configured or allowed to move proximally or distally independently ofouter plunger rod444, and in particular may be allowed to move distally throughouter plunger rod444 andplunger450. In some embodiments,plunger450 may be affixed to a distal end ofouter plunger rod444, so thatinner plunger rod446 may move through bothouter plunger rod444 andplunger450 without causing separation betweenouter plunger rod444 andplunger450. In further embodiments, a distal end ofouter plunger rod444 may simply contact or press againstplunger450.
• An initial configuration ofsyringe440 is depicted inFIG. 14A. As shown,inner plunger rod446,outer plunger rod444, andplunger450 are all located proximally from a volume ofdrug product454 contained withinbarrel442. As shown inFIG. 14B, upon depression of depressor orknob448, bothinner plunger rod446 andouter plunger rod444 may move distally throughbarrel442, consequently pushingplunger450 throughbarrel442. This may serve to prime the syringe, removing air and an excess quantity ofdrug product454 frombarrel442 by expelling it through, e.g., a distal end of barrel442 (via, e.g., a needle, cannula, tube, or other attachment at the distal end of barrel442). Distal movement of theplunger rods444,446 andplunger450 may eventually be halted by contact betweenplunger450 and insert456. This may provide, e.g., a user with tactile, auditory, and/or visual feedback indicating that priming is complete.
• As shown inFIG. 14C,inner plunger rod446 may then be allowed to move distally independently fromouter plunger rod444, e.g., by rotation ofinner plunger rod446 such thatinner plunger rod446 disengages fromouter plunger rod444. Such rotation may, for example, cause threads on an exterior ofinner plunger rod446 to disengage from threads on an interior ofouter plunger rod444. In some embodiments, such rotation may allow forinner plunger rod446 to expand (e.g., telescope) distally.Inner plunger rod446 may then be moved distally throughchannel458, which may contain a volume ofdrug product454 suitable for a dosage amount. In this manner,inner plunger rod446 may be configured to expel a desired dosage amount ofdrug product454 through the distal end ofbarrel442. In some embodiments, a distal end ofinner plunger rod446 may include, be attached to, or be affixed to an inner plunger, which may be sized and configured to move distally throughchannel458, and push a volume ofdrug product454 suitable for a dosage amount towards and through the distal end ofbarrel442.
• Referring now toFIGS. 15A-15E, views of anothersyringe500 with a further embodiment of a dose expel control mechanism are depicted.Syringe500 may include abarrel502 and aplunger rod503 having a knob or depressor504 andprojections506,508 which extend in directions that are offset from one another.Plunger rod503 also includes astopper510. A proximal end ofbarrel502 is capped by a keyhole-shaped flange512 (a top-down view of which is depicted inFIG. 5E).Plunger514 is disposed in an interior ofbarrel502 such that it may be contacted and pushed distally byplunger rod503. The interior ofbarrel502 may also house a volume of adrug product516 located distally fromplunger514.
• An initial configuration ofsyringe500 is depicted inFIG. 15A. As shown, the plunger rod andplunger514 are located proximally from the volume ofdrug product516.Projections506, which extend to a distal end portion ofplunger rod503, are positioned so as to fit through the keyhole shape inflange512, allowingplunger rod503 to move distally untilflange512 contacts projections508 (FIG. 15B). The extent of the distal movement allowed in this configuration may be sufficient toprime syringe500 and remove air betweenplunger514 anddrug product516. As shown inFIG. 15B,plunger rod503 may be prevented from moving further by the contact betweenflange512 andprojections508, which may be of a similar shape and size toprojections506, but in a different configuration from projections506 (e.g., a rotationally offset configuration).
• FIG. 15C depictssyringe500 upon the rotation ofplunger rod503 by 90 degrees. In this configuration,projections508 may now fit throughflange512, as shown inFIG. 15D.Plunger rod503 may then move distally until its movement is stopped bystopper510, which may have a shape and/or size that is not configured to fit throughflange512 in any orientation. Movement ofplunger rod503 as shown fromFIG. 15C toFIG. 15D may dispense a volume ofdrug product516 equivalent to a suitable or desired dose for a patient (e.g., by a needle, cannula, tube, or other attachment to the distal end of syringe500). Whileplunger rod503 is depicted asrotation 90 degrees betweenFIGS. 15C and 15D, it is understood thatprojections506 and508 may be rotationally offset by any suitable amount.
• In some embodiments, as shown inFIG. 15D, upon dispensing the desired or suitable volume ofdrug product516,plunger514 may not be flush with a distal end of the interior ofbarrel502 and a volume ofdrug product516 may remain inbarrel502. In some embodiments, this may allow for increased accuracy in the volume of dose delivered fromsyringe500, as discrepancies in size or shape betweenstopper514 and the distal end ofbarrel502 will not prevent the desired or suitable dose volume from being dispensed. Moreover, this (and other embodiments herein) may eliminate the need for a dose line onsyringe500, which may reduce or eliminate inaccuracies that may occur when placing a dose line onbarrel502 during manufacturing, and/or when visually gauging whether a volume ofdrug product516 is aligned with a dose line onbarrel502.
• It should be noted that whileprojections506,508 are depicted as having a particular shape and size, it is contemplated that they and the corresponding opening inflange512 may have any suitable shape and size allowing for passage ofprojections506,508 throughflange512. Moreover, it should be noted that while an opening is being shown inflange512, any suitably shaped opening may be incorporated in any part ofsyringe500 suitable to regulate movement of plunger rod503 (e.g., into a finger flange, a stopper fixed at a proximal end portion ofbarrel502, a proximal side ofbarrel502, or any other suitable portion of syringe500).
• Referring now toFIGS. 16A-16E, views of anothersyringe600 with a further embodiment of a dose expel control mechanism are depicted.Syringe600 may include abarrel602 and aplunger rod603 having adepressor604 and aprojection606. Aplunger608 is disposed in an interior ofbarrel602. Aremovable key610 is disposed at a proximal end ofbarrel602. The interior ofbarrel602 may also house a volume of adrug product612. A proximal end ofbarrel602 may be closed or closed off in any suitable manner, having an opening configured to allow passage of the thin portion ofplunger rod603.
• In some aspects of this embodiment,projection606 may be sized and configured such that it is unable to pass beyondkey610. Thus,plunger rod603 may only be depressed distally untilprojection606 contacts key610.Projection606 may be affixed toplunger rod603 in any suitable manner, or may be of a piece with (e.g., molded as a part of)plunger rod603.
• In some embodiments, key610 may be made as a separate structure from other aspects ofsyringe600. In further embodiments, key610 may be of a piece with another component ofsyringe600, such as, e.g., a removable finger flange (not shown).
• An initial configuration ofsyringe600 is depicted inFIG. 16A. As shown,plunger rod603 andplunger608 are located proximally from the volume ofdrug product612 disposed in the interior ofbarrel602.Projection606 is located a distance proximally fromkey610. As shown inFIG. 16B,plunger rod603 may be allowed to move distally (e.g., via depression of depressor604) untilprojection606 contacts key610. The extent of the distal movement allowed in this configuration may be sufficient toprime syringe600 and remove air betweenplunger608 anddrug product612. As shown inFIG. 16B,plunger rod603 may be prevented from moving further by the contact betweenkey610 andprojection606.
• FIG. 16C depictssyringe600 upon removal ofkey610. A height ofkey610 may be proportional to a desired or suitable dosage volume ofdrug product612, such that oncekey610 is removed,plunger rod603 andprojection606 are free to move further distally untilprojection606 contacts, and is obstructed by, a proximal end of barrel602 (FIG. 16D) or other component ofsyringe600 located at a distal end portion of barrel602 (e.g., a flange, lid, or stopper). This movement ofplunger rod603 allows forplunger608 to likewise expel a desired or suitable dosage volume of drug product612 (e.g., via needle, cannula, tube, or other mechanism connected to a distal end of syringe600).
• Referring now toFIGS. 17A-17B, two schematic views of additional embodiments of delivery devices with dose expel control mechanisms are depicted.FIG. 17A depicts asyringe700a, having abody702, aplunger rod704 with a plurality of teeth, aplunger706, and a volume ofdrug product708. The teeth ofplunger rod704 may be configured to engage with complementary teeth on anintermediate gear712, which may in turn be configured to engage with teeth on adriving gear714a. Drivinggear714ais depicted with two longer teeth, which are configured to engage with tabs on an offset actuator710a.
• Priming and dispensing of a dose fromsyringe700amay both be accomplished by depression of offset actuator710a(e.g., to a first depressed position and a second depressed position). The tabs of offset actuator710amay be sized and configured to interact with (e.g., push on) the long teeth of drivinggear714aat desired intervals corresponding to priming ofsyringe700a(the lower tab and a first of the long teeth of drivinggear714aand dispensing of a desired dosage amount of drug product708 (the upper tab of actuator710aand a second of the long teeth of drivinggear714a.FIG. 17A depicts, for example, a position of drivinggear714aand actuator710aaftersyringe700ahas been primed (e.g., a first depressed position). In some embodiments, drivinggear714a,intermediate gear712, orplunger rod704 may be configured to provide audio, visual, or tactile feedback upon movement of actuator710ato a first or second depressed position (e.g., by providing a clicking sound, or by resisting movement beyond the depressed position). In some embodiments, the interaction between actuator710aanddriving gear714amay resemble that of a Geneva drive. In some embodiments, rotation of drivinggear714amay be stopped by contact between a long tooth of drivinggear714aandintermediate gear712.
• Multiple configurations of a driving gear and an actuator are possible in order to achieve priming and/or drug dispensing steps by depression of the actuator. For example,FIG. 17B depicts asecond syringe700bwith adriving gear714bhaving three long teeth, instead of two, and an actuator710bhaving three tabs, instead of two. In such an embodiment, it is contemplated that actuator710bmay be depressed multiple times (e.g., to a first depth, a second depth, and a third depth) to achieve a desired result (e.g., priming ofsyringe700b). Each contact between a tab of actuator710band a long tooth of drivinggear714bmay be accompanied by tactile, audio, or visual feedback, and may correspond with partially or fully primingsyringe700b, removing air bubbles fromsyringe700b, or dispensing a desired dose volume fromsyringe700b. In some embodiments, an actuator may have only one tab configured to interact with the long tooth or teeth of a driving gear (See, e.g.,actuator710cand drivinggear714cdepicted inFIG. 17C).
• In some embodiments, an actuator may be spring-loaded, such that after depressing the actuator to a predetermined extent (e.g., enough for a tab of the actuator to push, contact, rotate, and/or otherwise interact with a single long tooth of the driving gear), the actuator may be returned to its pre-depressed location by, e.g., a spring return or other return mechanism. Such an embodiment is schematically depicted inFIG. 17C, where depression ofactuator710cmay compressspring716, which may inturn cause actuator710cto return to its pre-depressed location upon release. When actuator710cis depressed again to a predetermined extent, the tab onactuator710cmay push, contact, rotate, and/or otherwise interact with another single long tooth of the driving gear. Each depression of the actuator may serve a separate function (e.g., to prime and/or remove air from a syringe, or to dispense a suitable dosage volume from a syringe).
• WhileFIGS. 17A-17C depict potential versions of embodiments including a driving gear and an actuator, many more permutations and combinations of driving gears having longer teeth and actuators having tabs are contemplated. Additional variations on these embodiments include that the actuator (e.g.,actuator710c) may be spring-loaded or otherwise configured in any suitable manner to return to an initial position after, e.g., completing a priming or dispensing step.
• Referring now toFIGS. 18A-18F, views of another embodiment of a dose expel control mechanism are depicted.FIGS. 18A and 18B depict a front view and an angled view, respectively, of asleeve800.Sleeve800 may be configured to surround and/or attach to, e.g., a syringe barrel, and may include abody801, achannel802, aflange804, and an offsetportion806 ofchannel802.Sleeve800 may be configured to be used in conjunction with aplunger rod820, depicted in, e.g.,FIG. 18C.Plunger rod820 may include aprimary body822 extending from acap826.Primary body822 may be configured to extend into a body of a syringe barrel. Plungerrod pin arm824, which may extend fromcap826 separately fromprimary body822, may be configured to extend adjacent to a syringe barrel into whichprimary body822 is extending.Plunger rod end828 may be configured to contact, affix to, or otherwise attach to a plunger (not shown).
• FIG. 18D depicts asyringe assembly830 includingsleeve800 andplunger rod820 surrounding asyringe832. As shown, plungerrod pin arm824 may be sized and configured to slide throughchannel802. Asplunger rod820 is depressed distally into the body ofsyringe832, plungerrod pin arm824 may move distally throughchannel802. When plungerrod pin arm824 reaches the offsetportion806 ofchannel802, the shape ofchannel802 may stop further progress ofplunger rod820 distally.FIG. 18E depicts that, upon rotation of plunger rod820 (e.g., turning of cap826) or separate movement or rotation of plungerrod pin arm824, plungerrod pin arm824 may move laterally into offsetportion806 ofchannel802, after which further distal movement of plungerrod pin arm824, and thusplunger rod820, may be possible.
• Syringe832 may include a volume of a drug product that may be greater than or equal to a desired dose for a patient. Initial distal movement of plunger rod820 (e.g., prior to plungerrod pin arm824 approaching offsetportion806 of channel802) may be used toprime syringe832. Contact of plungerrod pin arm824 with the change in shape ofchannel802 near offsetportion806 of channel802 (shown in, e.g.,FIG. 18E) may signify that the syringe is primed and that air has been removed from an interior ofsyringe832. A length of offsetportion806 ofchannel802 may be proportional to a desired dosage volume of a drug product insidesyringe832 aftersyringe832 has been primed. Thus, rotation ofplunger rod820 to align plungerrod pin arm824 with offsetportion806 ofchannel802, and subsequent depression ofplunger rod802 such that plungerrod pin arm824 slides through off setportion806, may result in delivery of the desired dose of a drug product through the distal end of syringe832 (depicted in, e.g.,FIGS. 18E and 18F as being coupled to a needle).
• FIG. 18F depicts a detail cross-sectional side view ofassembly830. Plungerrod pin arm824 is shown as having contacted the portion ofchannel802 where offsetportion806 begins. As such,assembly830 may be in the “primed” position. Theinterior834 ofsyringe832 indicated inFIG. 18F may correspond to a desired dose volume of a drug product for delivery to a patient.
• Referring now toFIGS. 19A-19E, views of another embodiment of a dose expel control mechanism are depicted.Assembly900 may include asyringe body902, aplunger rod904a, aplunger906, a plungerrod pin arm908, and asleeve910a, which may be connected to asleeve flange912.Syringe body902 may house a volume ofdrug product914 located distally fromplunger906. Operation of this embodiment may be similar to operation ofassembly830 depicted inFIGS. 18A-18F. Notably,sleeve910aneed not extend along a full length ofsyringe body902, allowing for visibility ofsyringe body902, or intosyringe body902 ifsyringe body902 is transparent. A length ofsleeve910a(and/or other parts of assembly900) may be chosen to, e.g., help with ease of handling ofassembly900.
• As depicted inFIGS. 19A-D, various configurations of a sleeve and a channel in the sleeve may be used in conjunction withassembly900, to allow for priming and dispensing of a desired dose of a drug product fromassembly900. For example,sleeve910adepicted inFIG. 19A includes achannel909awhich does not extend through the entirety ofsleeve910a. In this embodiment, the upper portion ofchannel909amay correspond to a distance that plungerrod pin arm908, and thus thatplunger rod904a, may travel in order toprime assembly900, and the offset lower portion ofchannel909amay be proportional to a desired dosage volume ofdrug product914 that may be dispensed from a distal end ofassembly900 by rotation and distal movement ofplunger rod904auntil plungerrod pin arm908 is stopped from further distal movement by the end ofchannel909a. The closed end ofchannel909aensures that more than the desired dosage volume is not delivered, and may mitigate variance in, e.g., a desired dosage volume by preventingplunger906 from moving distally into a tapered distal end portion ofsyringe body902. Such variance may be caused by, e.g., variability in geometries ofplunger906 andsyringe body902.
• In alternative embodiments, the sleeve may have different configurations such as those depicted inFIGS. 19B-19D. Each ofFIGS. 19B-19D depict a cross section of a sleeve having a variation of a channel through which plungerrod pin arm908 may travel, thus guiding movement ofplunger rod904awithinsyringe body902. For example,FIG. 19B depicts a front view of a half-sleeve910b. Half-sleeve910bmay not wrap aroundsyringe body902 to create a narrow channel through which plungerrod pin arm908 may travel; instead, plungerrod pin arm908 may be guided by the “open” wall of half-sleeve910b, and may travel inarea909badjacent to the open wall of half-sleeve910b.Sleeve910c, depicted inFIG. 19C, provides a configuration similar to that ofsleeve910a, except for the open end ofchannel909c, as opposed to the closed end ofchannel909a. Such a configuration may allow for, e.g., bottoming out ofplunger906 insyringe body902, in embodiments in which such bottoming out would allow for dispensing a desired dose of a drug product fromassembly900.Sleeve910d, depicted inFIG. 19D, depicts achannel909dhaving a bend in a direction opposite to the bend ofsleeves910a,910b, and910c.
• FIGS. 19A-19D depict exemplary configurations of channels through which a plunger rod pin arm may travel. It is contemplated, however, that many more embodiments of sleeves and/or channels are possible. It is also contemplated that whilechannel909ais depicted as being disposed distally fromsleeve flange912, a channel (e.g., channel909a,909b,909c, or909d) may be incorporated into a sleeve on or near any portion of a syringe body (e.g., syringe body902), and/or may be incorporated into the syringe body itself (e.g., via embossing, engraving, molding, or other method).
• FIG. 19E depicts sleeve910C and an exemplary method or mechanism by which a sleeve (e.g.,sleeve910c) may connect to aflange portion912 during assembly. As shown,sleeve910cmay include one ormore tabs915 that may interface with complementary slots, holes, or indents913 inflange912. The interface betweentabs915 and slots, holes, or indents913 inflange912 may be any suitable interface allowing forflange912 andsleeve910cto connect (e.g., a dovetail connection, a dowel connection, a mortise and tenon connection, or any other now-known or future-developed type of connection). In alternative embodiments,flange912 may connect tosleeve910cwithout the use of tabs, slots, holes, or indents (e.g., using an adhesive, a heat connection, etc.).
• Attachment of the flange and sleeve in this manner may allow for one of the two components to be added tosyringe body902 first, followed by the other. For example,flange912 may be configured to slide, surround, snap on, or otherwise combine withsyringe body902, and the sleeve (e.g.,sleeve910a,910b,910cor910d) may subsequently be slid ontosyringe body902 and connected toflange912. As a further example, the sleeve may be added tosyringe body902 first, followed byflange912. In yet another example, the sleeve andflange912 may first be connected, and then may slide, surround, snap on or otherwise combine withsyringe body902.
• In further embodiments, a sleeve (e.g.,sleeve910a,910b,910cor910d) and flange (e.g., flange912) may be a unitary body (e.g., may be manufactured or molded together), instead of comprising two attached pieces. In some embodiments, the sleeve and/or flange may be made from, or may include, a material rigid enough to allow for a channel in the sleeve to restrict and/or control movement of a plunger rod pin arm, and flexible enough to allow for the sleeve and/or flange to snap onto or otherwise combine withsyringe body902. In some embodiments, for example, the sleeve and/or flange may include polypropylene. In some embodiments, for example, the sleeve and/or flange may include two different materials combined in an overmolding technique (e.g., polypropylene and a second material).
• Referring now toFIGS. 20A-20C, views of another embodiment of a dose expel control mechanism are depicted. All three are discussed in tandem herein. As shown primarily in the cross-sectional side view ofFIG. 20A and the cross section indicated by “A— A” depicted inFIG. 20B,assembly1000 may include aplunger rod1002, aplunger1003, asyringe body1004, a volume of adrug product1005 disposed withinsyringe body1004, aplunger rod arm1006 configured to extend from the plunger rod cap separately from, and parallel to,plunger rod1002, asleeve1008, asleeve pin1010, a spring-loadedpin casing1012, asleeve cavity1014, a plungerrod arm cavity1016, apin protrusion1018, and a sleeve pin slot1020 (depicted in the view ofsleeve1008 shown inFIG. 20C).
• As with the embodiments depicted inFIGS. 19A-19E,sleeve1008 may include a flange, and may be configured to wrap around a circumference ofsyringe body1004.Assembly1000 differs from, e.g.,assembly900 in thatplunger rod arm1006 does not include a pin; instead,plunger rod arm1006 may include acavity1016 into whichsleeve pin1010 may extend.Sleeve pin1010 may be slidably connected tosleeve1008 such that it extends throughpin slot1020. In some embodiments,pin casing1012, which may be spring loaded, may exert a force onsleeve pin1010 in a direction outward fromsleeve1008, while pin protrusion1018 (depicted in, e.g.,FIG. 20B) may preventsleeve pin1010 from being pulled out ofpin slot1020. In the configuration depicted inFIG. 20A,sleeve pin1010 may be pushed distally (e.g., towards the expulsion end of assembly1000) along the length ofpin slot1020 in order to moveplunger rod arm1006 distally (i.e., so thatplunger rod1002 also moves distally), becausesleeve pin1010 extends into plunger rod arm cavity1016 (depicted in, e.g.,FIG. 20B). This movement ofsleeve pin1010, and the corresponding movement ofplunger rod1002, may serve toprime assembly1000.
• Upon movement ofsleeve pin1010 to the distal end ofpin slot1020,pin protrusion1018 may become aligned withsleeve cavity1014, which may be sized and configured to housepin protrusion1018. The force exerted uponsleeve pin1010 bypin casing1012 may causepin protrusion1018 to be pulled intosleeve cavity1014, thus causingsleeve pin1010 to disengage from plungerrod arm cavity1016.
• Aftersleeve pin1010 has become disengaged from plungerrod arm cavity1016,plunger rod1002 may be pushed distally independently of sleeve pin1010 (e.g., by a user) to dispense a desired dosage ofdrug product1005.
• With respect to any embodiment in the present disclosure that includes a sleeve and a pin that may travel through a channel or slot in the sleeve, it is contemplated that the channel or slot need not necessarily be located within a sleeve. For example, in embodiments where a sleeve wraps fully or partially around a syringe or syringe body, the sleeve may be replaced by, e.g., a channel or slot being imprinted, molded, or otherwise disposed directly upon the syringe or syringe body.
• Features enumerated above have been described within the context of particular embodiments. However, features and aspects of the embodiments may be combined, added to other embodiments, subtracted from embodiments, etc. in any manner to assist with controlled preparation and/or delivery of a drug.
• Aspects of the embodiments above have been described with respect to priming doses and removing excess air bubbles from within syringes. However, aspects of these embodiments may also be employed for use with fillable syringes and multi-dose vials. For example, syringes according to the present disclosure may provide a more precise method for transferring drug product from a vial to a syringe. Precision during this syringe loading step may reduce or minimize overfilling of syringes from, e.g., vials of drug product. Inhibiting overfilling may in turn decrease wastage of a drug product and may increase or maximize the number of doses that may be administered from one vial.
• For example, to fillsyringe10 depicted inFIG. 1, dial5 may be rotated in the reverse direction to withdrawpiston8 intosyringe barrel9 away from the distal needle end to fillsyringe10 throughneedle13.
• As a further example, to fillsyringe60 depicted inFIG. 5,plunger rod61 may be rotated in the direction opposite to the direction needed toprime needle66 to withdrawpiston68 intosyringe barrel69 away from the distal needle end to fillsyringe60 throughneedle66.
• While a number of embodiments are presented herein, multiple variations on such embodiments, and combinations of elements from one or more embodiments, are possible and are contemplated to be within the scope of the present disclosure. Moreover, those skilled in the art will appreciate that the conception upon which this disclosure is based may readily be used as a basis for designing other devices, methods, and systems for carrying out the several purposes of the present disclosure.

Claims (21)

1-40. (canceled)

41. A drug delivery device comprising:

a barrel including a proximal end and a distal end;

a plunger rod extending into the barrel through an opening at the proximal end of the barrel, the plunger rod including a projection having a proximal portion and a distal portion; and

a flange coupled to the proximal end of the barrel, the flange including a body, an opening, a channel, a first surface, and a second surface that is distal of the first surface, wherein the first surface and the second surface define interfaces for engaging the distal portion such that the body is only configured for two longitudinal and distally-directed strokes of the plunger rod that are inhibited by the flange;

wherein the distal portion of the projection is positioned external from the body of the flange prior to an initial stroke of the plunger rod;

wherein, after the initial stroke, the distal portion abuts the first surface such that the flange limits distal movement of the plunger rod, wherein, upon rotating the plunger rod about the central longitudinal axis, the flange allows distal movement of the distal portion of the projection relative to the channel to allow the plunger rod to move until the distal portion abuts the second surface, wherein the second surface defines a closed end of the channel, the flange is configured to inhibit distal movement and rotation of the plunger rod relative to the barrel when the distal portion of the projection is positioned against the closed end of the channel;

wherein the proximal portion of the projection is longitudinally spaced from the first surface when the distal portion abuts the second surface such that the proximal portion is positioned outside and proximal to the flange.

42. The drug delivery device ofclaim 41, wherein, prior to the initial stroke, the distal portion of the projection is spaced from the first surface of the flange by a priming distance.

43. The drug delivery device ofclaim 42, wherein the initial stroke includes advancing the plunger rod distally by the priming distance until the distal portion of the projection contacts the first surface of the flange.

44. The drug delivery device ofclaim 42, wherein upon moving the initial stroke and rotating the plunger rod about the central longitudinal axis and relative to the flange, the plunger rod is configured to move distally relative to the flange via a final stroke.

45. The drug delivery device ofclaim 44, wherein the projection is longitudinally aligned with the first surface and longitudinally misaligned with the second surface, in a direction parallel to the central longitudinal axis, upon the plunger rod moving the initial stroke and prior to rotating about the central longitudinal axis.

46. The drug delivery device ofclaim 44, wherein the projection is longitudinally aligned with the second surface and longitudinally misaligned with the first surface, in a direction parallel to the central longitudinal axis, upon rotating the plunger rod about the central longitudinal axis and moving along the final stroke.

47. The drug delivery device ofclaim 41, further comprising a plunger inside the barrel and in contact with the plunger rod;

wherein movement of the plunger rod via the initial stroke and the final stroke does not cause the plunger to contact the distal end of the barrel.

48. A drug delivery device comprising:

a barrel including a proximal end and a distal end;

a plunger rod extending into the barrel through an opening at the proximal end of the barrel and along a central longitudinal axis of the drug delivery device, the plunger rod including a projection having a proximal portion and a distal portion; and

a flange coupled to the proximal end of the barrel, the flange including a body, and a channel;

wherein the distal portion of the projection is longitudinally spaced apart from a first proximally-facing surface of the flange and positioned external from the flange prior to an initial stroke of the plunger rod;

wherein the flange at least partially defines a first path terminating at the first proximally-facing surface, such that the first proximally-facing surface abuts the distal portion after the plunger rod moves the initial stroke through the first path of the flange, wherein the channel is defined by a second proximally-facing surface that is longitudinally offset from the first proximally-facing surface, the channel is only configured for one stroke that is inhibited by the flange after the initial stroke that causes the distal portion to abut the first proximally-facing surface;

wherein the flange defines a second path at least partially defined by sidewalls of the channel, and terminating at the second proximally-facing surface, such that the second proximally-facing surface abuts the distal portion after the plunger rod moves a final stroke through the second path of the flange, the flange is configured to inhibit distal and rotational movement of the plunger rod relative to the barrel with the distal portion of the projection positioned against the second proximally-facing surface; and

wherein the second proximally-facing surface is configured to receive the distal portion of the projection with the proximal portion of the projection positioned outside and proximal to the flange.

49. The drug delivery device ofclaim 48, wherein the body of the flange has a one-piece construction, and includes a hole having a circumference that is fully enclosed by the body.

50. The drug delivery device ofclaim 48, wherein the flange is a finger flange and includes a sleeve defining the first proximally-facing surface and the second proximally-facing surface.

51. The drug delivery device ofclaim 50, wherein the sleeve is integral with the flange such that the finger flange and the sleeve are a unitary body.

52. The drug delivery device ofclaim 50, wherein the first proximally-facing surface is positioned proximal to, and laterally offset from, the second proximally-facing surface.

53. The drug delivery device ofclaim 48, wherein the projection is disposed about, and protrudes in a direction perpendicular to, the central longitudinal axis of the drug delivery device.

54. A method of preparing the drug delivery device ofclaim 48 for delivering a dose of a drug substance, the method comprising:

advancing the plunger rod distally into the barrel via the initial stroke until the distal portion abuts the first proximally-facing surface; and

rotating the plunger rod about the central longitudinal axis, relative to the flange, until the distal portion no longer abuts the first proximally-facing surface.

55. The method ofclaim 54, the method further comprising:

advancing the plunger rod distally into the barrel via the final stroke until the distal portion abuts the second-proximally facing surface.

56. The method ofclaim 55, wherein advancing the plunger rod via the initial stroke primes the drug delivery device, and advancing the plunger rod via the final stroke delivers the dose of the drug substance from the drug delivery device.

57. A drug delivery device comprising:

a barrel including a proximal end and a distal end;

a plunger rod extending into the barrel, wherein the plunger rod includes a projection that has a proximal portion and a distal portion; and

a flange coupled to the proximal end of the barrel, the flange including a body, an opening, a channel, a first surface, and a second surface that is distal of the first surface, the flange is configured to receive the plunger rod through the opening and the projection through the channel;

wherein, the body is only configured for a pair of distally-directed strokes of the plunger rod that is inhibited by the flange;

wherein, when:

the distal portion of the projection is longitudinally spaced from the first surface by a first distance corresponding to a first stroke of the pair of distally-directed strokes, the distal portion is not in longitudinal alignment with the second surface;

the distal portion of the projection contacts the first surface of the flange, the distal portion is not in longitudinal alignment with the second surface of the flange;

the distal portion of the projection is longitudinally spaced from the second surface by a second distance corresponding to a second stroke of the pair of distally-directed strokes, the distal portion is in longitudinal alignment with the second surface and not in longitudinal alignment with the first surface; and

the distal portion of the projection contacts and is in longitudinal alignment with the second surface, the proximal portion of the projection is longitudinally spaced from the first surface and positioned proximal to the opening and outside the flange;

wherein the second surface defines a closed end of the channel, and the flange is configured to inhibit distal movement and rotation of the plunger rod relative to the barrel when the distal portion of the projection is positioned against the closed end of the channel.

58. The drug delivery device ofclaim 57, further comprising:

a plunger disposed inside the barrel and in contact with the plunger rod;

wherein, when the projection is in contact with the first surface and the second surface, the plunger is not flush with the distal end of the barrel.

59. The drug delivery device ofclaim 57, further comprising:

a plunger disposed inside the barrel and in contact with the plunger rod;

a first volume of drug product disposed in between the plunger and the distal end of the barrel prior to the plunger rod moving the first stroke;

a second volume of drug product disposed in between the plunger and the distal end of the barrel after the plunger rod moves the first stroke and prior to moving the second stroke, wherein the second volume of drug product is smaller than the first volume of drug product; and

a third volume of drug product disposed in between the plunger and the distal end of the barrel after the plunger rod moves the second stroke, wherein the third volume of drug product is smaller than the second volume of drug product and greater than zero.

60. The drug delivery device ofclaim 57, wherein the first distance is less than the second distance, and the plunger rod is prevented from moving distally relative to the flange after the projection contacts the second surface.

Images